The present application incorporates U.S. Pat. No. 7,879,372 issued Feb. 1, 2011 herewith in its entirety.
1. Field of the Invention
This invention relates to the treatment of diseases and conditions associated with inflammation of the inner ear of a mammal, e.g. humans or pets, caused by asteatosis or “dry ear” comprising applying a semi-viscous, lipid base formulation with hydrocortisone to the affected tissue.
2. Related Art
Asteatosis, known as “dry ear”, is a common condition of the external auditory canal where the skin, tissue, and fibrocartilaginous surfaces of the ear canal are dry and lack cerumen production and protection. This condition is sometimes associated with aging, over-cleaning, or chronic conditions such as diabetes or other serious diseases or conditions.
The cerumen earwax lubricates and prevents desiccation and burning of the skin within the ear canal, or external ear and middle ear (known as asteatosis). Because of the lack of cerumen which is protective of the ear canal, there is a change in the moisture balance and pH of the canal which may make it more prone to external ear infection causing dryness or desiccation of the canal skin leading to itching, scratching, and irritated ear canal surfaces. Antimicrobial protective properties of cerumen are due principally to the presence of fatty acids and a slightly acidic pH ˜6. The lubricative properties of cerumen arise from the high content of the sebum produced by the sebaceous glands. Wet earwax, or cerumen, may contain lipids including, squalene, long-chain fatty acids, and alcohols. Pathogenic and nonpathogenic bacteria and fungi may dominate the flora of the canal causing over-growth and actual infection. These infections can often time be very difficult to clear up requiring multiple office visits, particularly if there is fungal overgrowth. It is at this point that many patients will insert cotton tip applicators and other foreign bodies in the canal to alleviate the discomfort thereby stripping the protective coating of earwax that protects the skin lining of the ear canal. As a result, the ear canal may suffer from atopic dermatitis, desiccation, or more serious skin infection such as otitis external. Traditionally, patients seek medical assistance after the infection has occurred.
Another type of otitis externa that occurs mainly in elderly diabetics can develop due to a severely compromised immune system. Malignant otitis externa infects the bony ear canal and the soft tissues deep to the bony canal creating an unrelenting and inoperable pain. It must be treated with antibotics or it can spread deeper into the head and involve the bones of the skull base, constituting skull base osteomyelitis.
Conductive hearing loss happens when there is a problem conducting sound waves anywhere along the route through the outer ear, eardrum, or middle ear. It is presumed high frequencies produce a large vibration at the end near the middle ear, the eardrum detects and simplifies incoming air pressure waves for loudness, and the basilar membrane of the inner ear separates out different frequencies in a human. The physical condition of the ear, including the ear canal skin, tissue, and fibrocartilaginous surfaces should be maintained for overall healthy ear and sound recognition and preventing infection or ear disorders.
“Swimmer's ear”, or ear ache, symptoms include swelling of the ear canal which may not be present in “dry ear” symptoms and ear canal tissue conditions. Ear inflammation is typically reported with “swimmer's ear” whereby a swimmer receives contaminated water or retains moisture in the ear causing it to succumb to microbial growth (most often pseudomonas) and the use of alcohols and drying solvents to treat this condition are described in the prior art (see Fust US 2004/0101506, Kogure U.S. Pat. No. 4,961,927, and Redmond U.S. Pat. No. 6,818,232). Fust teaches a method and composition for treating otitis externa, swimmer's ear, which soothes irritated ear canals and reduces inflammation. Fust (US 2004/0101506) focuses on the treatment of swimmer's ear, infection and some of its many bacteria or fungi forms, earwax, ear pressure and hearing loss, adverse reactions to antibiotics, all which result in symptoms similar to swimmer's ear (paragraphs [0001-0006]). There is a lack of predictability or exactness in prior art and correlation between the symptoms, diseases, and cures for ear treatment. “A wide variety of protocols for treating otitis externa may be complicated with immune system response and complications in treating “swimmer's ear” and cannot be routinely optimized” (FUST paragraphs [0007 through 0009]). “While the medical community has a wide variety of protocols available for the symptomatic treatment of otitis externa and other bacterial and/or fungi related diseases, it appears that little or no attention has been given to prevention of the disease. Fust teaches a wide variety of organisms and/or complicated conditions are commonly labeled “swimmer's ear” including a list of over 43 known organisms that cause otitis externa (paragraph [0002]). There is speculation in equating “swimmer's ear”, or ear ache, with “dry ear” symptoms.
In treating the desiccation of skin surfaces and the absorption or adsorption of the medication, the base of a topical medication is often as important as the medication itself. A medication's potency often is changed with its base. It is important to receive a medication applied to the skin, in the correct base, for example as a liquid topical solution, lotion, cream, or ointment. Manufacturers of each topical product have control over the content of the base of a medication.
Many base topical solutions and mixtures for removing water from and drying the ear canal include drying alcohols such as isopropanol. Alcohol is a common liquid base used to clean out the ear, especially of pets, because it dissolves the natural oils and fats present in the ear, but alcohol is also drying, leaving the ear and skin red and irritated. Alcohol evaporates quickly removes water and thereby often over-dries the ear tissue and leaves it red and irritated.
Additionally, a mixture of acetic acid and water or acetic acid and alcohol are also common liquid bases used to clean ears, for example drops containing dilute acetic acid (vinegar diluted 3:1). While such mixtures are effective in killing bacteria and in eliminating yeast infections, they are not pH balanced, may over-dry, and may irritate or actually burn ear tissues.
Another topical solution liquid base, hydrogen peroxide, is also often used as an oxidizer or drying agent, and is an anti-microbial disinfectant used as a medical and oral debriding agent and for cleaning wounds and removing dead tissue. Hydrogen peroxide is absorbed by skin upon contact and creates a local skin capillary embolism that stops wound bleeding which appears as a whitening of the skin. Hydrogen peroxide, however, is not an effective solvent for dissolving ear waxes and oils.
In addition, most of these “drying” topical solvent liquid base ear drops require the user to remain in awkward sideways positions for dispersing of medication to the ear canal until the liquid solvent dries.
Ointments are base formulations usually homogeneous mixtures, very moisturizing with ˜80% oil to 20% water, and are beneficial for dry skin conditions. They have a low risk of sensitization due to formulations having few compounds or ingredients, beyond the base oil or fat, and low irritation risk. There are many general designed classes of mixtures, with no clear dividing line between similar formulations therefore what might be labeled “cream” is in fact an “ointment”. They are often disliked by patients due to greasiness.
A cream base formulation typically contains an emulsion of oil and water in almost equal proportions. Creams are user-friendly soft solids or liquids thicker than a lotion and contain medicaments for therapeutic purposes. A cream maintains its shape when removed from its container. Many topical steroid creams are oil-in-water emulsions which penetrate the outer layer of skin. Emulsions are chemical mixtures produced by mechanical blending or mixing of components, may be heterogenous in nature, and may easily be disposed to phase separation of components. Since creams are partially water-based, there is a potential for bacterial growth, contamination, or reduced shelf life of the medicament. Sensitivity to antibiotics and/or the preservatives contained in cream based medicaments is often reported. Adverse reactions to topical hydrocortisone (Cortisol) include burning, itching, irritation, dryness, dermatitis, endocrine side effects, and may affect persons with diabetes or glaucoma since a primary function of hydrocortisone in the body is increasing blood sugar through gluconecogenesis. For example, Cortisporin is available as a cream for ear treatment. It is a combination of two antibiotics Neomycin and Polymyxin B for treating ear canal bacterial infections and the corticosteroid hydrocortisone for reducing inflammation. Reported sensitization reactions to antibiotic neomycin may cause skin sensitization, swelling, or sensitivities of the kidney (nephrotoxicity), cochlea (ear) or auditory nerves (ototoxicity), or may induce excessive glutamate or calcium production (excitotoxicity).
Lotions include liquid base formulations similar to topical solutions but are thicker and more emollient than solvent solutions. Often a lotion contains an oil mixed with water, little to no alcohol, and should be shaken into suspension before use. A colloidal suspension may be a mixture, as an emulsion, where small but undissolved solid particles are suspended and dispersed by molecular motion in the surrounding solvent system.
Lipids are a broad group of naturally occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins, glycerols, and glycerides. Lipids are usually liquid greasy to the touch, soluble in alcohol or ether, insoluble in water, and hydrophobic or amphiphilic molecules. Lipids are basic structural components of living cells and store energy.
Emulsion lotions are a type of suspended solution in which surface tension plays a role between two liquids. Emulsions are also used in making many cosmetic products, or liquid preparations consisting of completely immiscible liquids, one of which forms globules dispersed throughout the other liquid.
Cationic emulsions are used in some pharmaceutical products because of their antimicrobial properties. A colloidal suspension may be a mixture where small but undissolved particles are suspended and dispersed by molecular motion in the surrounding solvent system. Non-ionic emulsions are used in some pharmaceutical products because they have low toxicity. For example, tiny fragments of oil suspended in pure water will spontaneously assemble themselves into much larger masses. Dispersion processes are not well understood and are not purely chemical but are also mechanical. Dispersion is a process by which, in the case of solids, particles become widely or evenly spread throughout a liquid. The smaller the droplet, the greater the surface tension and thus the greater the force to merge with, or perhaps to encapsulate, other lipids. Surfactants decrease surface tension of liquids. Surfactants are usually organic compounds that are amphiphilic, meaning they contain both hydrophobic structural groups and hydrophilic structural groups. Therefore, a surfactant molecule contains both a water insoluble (or oil soluble component) and a water soluble component.
Steroids or sterols are lipids and include any fat-soluble organic compounds derived from plants or animals with specific physiological action. Hydrocortisone is a steroid hormone, or glucocorticoid, produced by the adrenal gland. It is released in response to stress and low blood levels of glucocorticoids to increase blood sugar through gluconeogenesis and counteracts insulin. Hydrocortisone suppresses the immune system, aids in fat, protein and carbohydrate metabolism, and acts as a diuretic hormone. Hydrocortisone is an anti-inflammatory which functions by reducing histamine secretion and stabilizes lysosomal membranes preventing damage to healthy tissue.